Correia Ana S, Pereira Sara C, Morais Tiago, Martins Ana D, Monteiro Mariana P, Alves Marco G, Oliveira Pedro F
LAQV-REQUIMTE and Department of Chemistry, Campus Universitario de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.
Endocrine and Metabolic Research, Unit for Multidisciplinary Research in Biomedicine, Department of Anatomy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Biomedicines. 2022 Oct 17;10(10):2609. doi: 10.3390/biomedicines10102609.
: Calorie restriction (CR) diets and glucagon-Like Peptide-1 (GLP-1) analogs are known to alter energy homeostasis with the potential to affect the expression of obesity-related genes (ORGs). We hypothesized that CR and GLP-1 administration can alter ORGs expression in spermatozoa and testes, as well as the sperm parameters implicated in male fertility. Six-week-old adult male Wistar rats (n = 16) were divided into three groups, submitted either to CR (n = 6, fed with 30% less chow diet than the control rats), GLP-1 administration (n = 5, 3.5 pmol/min/kg intraperitoneal) for 28 days, or used as controls (n = 5, fed ad libitum). Selected ORGs expression, namely the fat mass and obesity-associated (), melanocortin-4 receptor (), glucosamine-6-phosphate deaminase 2 (), and transmembrane protein 18 () were evaluated in testes and spermatozoa by a quantitative polymerase chain reaction (qPCR). CR resulted in lower body weight gain and insulin resistance, but a higher percentage of sperm head defects. GLP-1 administration, despite showing no influence on body weight or glucose homeostasis, resulted in a lower percentage of sperm head defects. CR and GLP-1 administration were associated with a higher expression of all ORGs in the testes. Under CR conditions, the genes and expression in the testes and the and transcripts abundance in sperm were positively correlated with the spermatozoa oxidative status. The abundance of and in the spermatozoa of rats under CR were positively correlated with sperm concentration, while the testes' expression was also positively correlated with sperm vitality and negatively correlated with insulin resistance. Testes expression was negatively correlated with sperm head defects. CR and GLP-1 administration results in higher ORGs expression in testes, and these were correlated with several alterations in sperm fertility parameters.
已知热量限制（CR）饮食和胰高血糖素样肽-1（GLP-1）类似物会改变能量平衡，有可能影响肥胖相关基因（ORGs）的表达。我们推测，CR和GLP-1给药可改变精子和睾丸中ORGs的表达，以及与男性生育能力相关的精子参数。将六周龄成年雄性Wistar大鼠（n = 16）分为三组，分别接受CR（n = 6，喂食量比对照大鼠少30%的饲料）、GLP-1给药（n = 5，3.5 pmol/分钟/千克腹腔注射）28天，或用作对照（n = 5，自由进食）。通过定量聚合酶链反应（qPCR）评估睾丸和精子中选定的ORGs表达，即脂肪量和肥胖相关基因（FTO）、黑皮质素-4受体（MC4R）、氨基葡萄糖-6-磷酸脱氨酶2（GNPDA2）和跨膜蛋白18（TMEM18）。CR导致体重增加和胰岛素抵抗降低，但精子头部缺陷百分比更高。GLP-1给药尽管对体重或葡萄糖稳态没有影响，但导致精子头部缺陷百分比降低。CR和GLP-1给药与睾丸中所有ORGs的较高表达相关。在CR条件下，睾丸中FTO和GNPDA2基因的表达以及精子中MC4R和TMEM18转录本的丰度与精子氧化状态呈正相关。CR大鼠精子中MC4R和TMEM18的丰度与精子浓度呈正相关，而睾丸中FTO的表达也与精子活力呈正相关，与胰岛素抵抗呈负相关。睾丸中GNPDA2的表达与精子头部缺陷呈负相关。CR和GLP-1给药导致睾丸中ORGs表达更高，并且这些与精子生育参数的几种改变相关。
